Colonic mucosal mediators from patients with irritable bowel syndrome excite enteric cholinergic motor neurons

• Published in: Neurogastroenterology and motility Vol. 24; no. 12; pp. 1118 - e570
• Main Authors: Balestra, B., Vicini, R., Cremon, C., Zecchi, L., Dothel, G., Vasina, V., De Giorgio, R., Paccapelo, A., Pastoris, O., Stanghellini, V., Corinaldesi, R., De Ponti, F., Tonini, M., Barbara, G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-12-2012; Wiley Subscription Services, Inc
• Subjects: Adult; Animals; Antagonists; Biopsy; Capsaicin receptors; capsazepine; Cell activation; Cells; Cholinergic Neurons - metabolism; Colon; Colon - immunology; Colon - metabolism; Colon - pathology; Culture Media, Conditioned - pharmacology; Enteric nervous system; Female; Guinea Pigs; Humans; Hypersensitivity; Inflammation; inflammatory mucosal mediators; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Irritable bowel syndrome; Irritable Bowel Syndrome - immunology; Irritable Bowel Syndrome - metabolism; Irritable Bowel Syndrome - pathology; Male; Mast cells; Mast Cells - immunology; Mast Cells - metabolism; Mast Cells - pathology; Motor neurons; Motor Neurons - metabolism; Mucosa; Muscles; myenteric plexus; Myenteric Plexus - metabolism; Neurons; prostaglandin D2; prostaglandin receptors; Purine P2X receptors; Rodents; Serine proteinase; twitch contractions
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.12000

Background  Mediators released in the mucosal milieu have been suggested to be involved in visceral hypersensitivity and abdominal pain in patients with irritable bowel syndrome (IBS). However, their impact on myenteric neurons remains unsettled.
Methods  Mucosal biopsies were obtained from the descending colon of patients with IBS and controls. Mucosal mast cells were identified immunohistochemically. The impact of spontaneously released mucosal mediators on guinea pig electrically stimulated longitudinal muscle myenteric plexus (LMMP) preparations was assessed in vitro by means of selective receptor antagonists and inhibitors.
Key Results  Patients with IBS showed an increased mast cell count compared with controls. Application of mucosal mediators of IBS to LMMPs potentiated cholinergic twitch contractions, an effect directly correlated with mast cell counts. Enhanced contractions were inhibited by 50.3% with the prostaglandin D2 antagonist BW A868C, by 31.3% and 39% with the TRPV1 antagonists capsazepine and HC‐030031, respectively, and by 60.5% with purinergic P2X antagonist pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulfonic acid. Conversely, the serotonin1‐4, histamine1‐3, tachykinin1‐3 receptor blockade, and serine protease inhibition had no significant effect.
Conclusions & Inferences  Colonic mucosal mediators from patients with IBS excite myenteric cholinergic motor neurons. These effects were correlated with mast cell counts and mediated by activation of prostanoid receptors, TRPV1, and P2X receptors. These results support the role of mucosal inflammatory mediators and mast cell activation in altered motor function of IBS.